Preparation of 3-pyridols from 2-acylfurans



Patented Apr. 28, 1953 2,636,882 Pr ce PREPARATION OF 3-PYRIDOLS FROM Z-ACYLFURAN S Andrew P. Dunlop,

Swadesh, Maywood, 111.,

Riverside, and Samuel assignors to The Quaker Oats Company, Chicago, 111., a corporation of New Jersey No Drawing.

Application August 11, 1950,

Serial No. 178,998

6 Claims.

This invention relates to the preparation of pyridol compounds and more particularly to the preparation of 3-pyrido1s from 2-acylfurans.

We have found it possible to obtain good ultimate yields of 3-pyridols by reacting a 2-acylfuran with ammonia at elevated temperatures.

One object of the present invention is to provide an efiicient process for the preparation of 3-pyrido1s. Another object is to provide a process for the preparation of 3-pyridols in a direct manner which can be easily carried out using relatively inexpensive equipment. A very important object is to provide an improved process for producing B-pyridols by reacting a 2-acylfuran with ammonia. Other objects and advantages of the present invention will become apparent to those skilled in the art as the invention is more fully described.

Broadly stated, the present invention provides an improved process for the production of 3- pyridols which comprises heating a Z-acylfuran with ammonia in the presence of a solvent which is a good ionic medium, preferably water or an alcohol or a mixture of the two at elevated temperatures. In view of the fact that the particular Z-acylfuran used may be selected from a large list and since the best operating temperature depends largely upon the specific 2-acylfuran used, the temperatures employed may vary from about 100 to 200 C. Generally, we prefer to operate within a temperature range of 120 to 180 C. It is to be understood, however, that higher or lower temperatures may be used with a resultant increase or decrease in the reaction rate in accordance with the general law of chemical reactions. If the reaction is carried out in the absence of an added solvent the product is predominantly a 2-acylpyrro1e as is described in our copending application entitled Preparation of Z-acylpyrroles from 2-acy1furans, Serial No. 169,773, filed June 22, 1950. Actually the reaction can proceed in two directions, one the formation of the 2-acylpyrrole and two the formation of the B-pyridol. The formation of the later, however is favored by the presence of a solvent and as is evident from an inspection of the table below the better the solvent is as an ionic medium the higher the yield of 3-pyridol.

Reaction of Z-acetylfumn with ammonia Percent yield Solvent Pyrrole Pyridol The proportion of the reactants namely, the 2-acylfuran and ammonia used in our process may be varied over a wide range. Theoretically, in our process one mole of the Z-acylfuran reacts with one mole of ammonia in accordance with the following equation:

wherein Rzalkyl, aryl or furfuryl R'zalkyl, aryl, furfuryl or hydrogen In practice, however, we prefer to employ an excess of ammonia over the 2-acylfuran.

The products of our invention have been characterized as 3-pyridols by means of C, H, and N analysis, determination of neutral equivalents, by formation of the picrate derivatives and by the fact that these compounds produce a red color with F8C13 which is characteristic of phenolic compounds. 1

In order to disclose the nature of the present invention still more clearly, the following illustrative examples will be given in which parts by weight bear the same relation to parts by volume as do grams to cubic centimeters.

EXAMPLE 1 Preparation of Z-methyZ-S-pyridol To 25.3 parts by weight of Z-acetylfuran were added 293 and 300 parts by volume of 28% ammonium hydroxide and methanol respectively. After heating the solution for about 17 hours at a temperature of to C. in an autoclave, it was treated with 90 parts by weight of activated carbon in 3 equal increments and then concentrated at reduced pressure on a steam bath until crystal formation was observed. The mixture was cooled and then filtered. Further evaporation of the filtrate caused the precipitation of additional product. After combining this product with the first precipitate a total of 11.8 parts by weight of 2-methyl-3-pyridol was obtained representing a yield of 47 per cent of theory. The product had a melting point of 168.6 to 168.8 C. and the picrate derivative after recrystallizing from alcohol had a melting point of 201.6 to 201.8 C.

.'2 Rrcpamtz'on of 22-methyl-3-pynidol To 25.3 parts by weight of Z-acetylfuran were added 293 and 300 parts by volume of 28% ammonium hydroxide and water respectively. .=Af.ter heating the solution for about 17 hours at axtemperature of 140 to 160 C. in an autoclave, it was treated with 30 parts by weight 'of activated-carbon and then concentrated at reduced pressure on a steam bath until crystal formation was observed. The mixture was cooled and then filtered. Further evaporation of ithe filtrate caused the precipitation of additional product which after combining with the first precipitate gave a total of 11.9 parts.by weight of 2-methyl- 3 pyridol representing a4 '7 per cent yield of theory. i-No'pyrrole-formation was observed.

Preparation n) 2-.ethyl-3-pyridol To 30"partsby weight'of 2 propionylfuran were added 400 parts by volume each of 28% ammonium hydroxide and methanol. After heating the solution for about 20 hours at a ftemperature of 130 ito 140 C. in an autoclave, it was distilled under slightly reduced pressure until 600 parts by volume of methanol and water wereremoved. Benzene was then added to the solution and the distillation continued "until all the water was removed. "The-residualsolutioncontaining the ;3-,.pyridol in-benzene was treated with 20 parts by weight iof activated carbon :and then cooled. 5L8 parts thy weight of z-iethyl'amyridol M. B. 134.6 :"to i135k2 7C. 'was .obtained :as .a precipitate which represented :a .20 ,;per cent yield ofxtheory. Thepicrateederivative; after recrystallizingirom .alcohol :hada melting point {of ;17'1.7 to 172:3 .C.

Preparationo! z phcnyl-fiepym'dol 'I-o 25 parts by :weight or '2-ibenzoylfuran were added 196 and 300 parts by volume of 281% :ammon'ium hydroxide and methanol respectively.

After heating the mixture for about 22 1 hours ;at a temperature of 150 to 160 :C. .in anrautoclave, it was treated :with J60 iparts lby Weight of .ac-

tivated carbon in two equaltincrements: and :then concentrated at :reduced pressure on a :steam bath'until-cr-ystal formation was observed, :at the sametimeasmalllamountof dark oily liquid separated. The concentrated solution was -:cooled,

a small amount of amend added to .redissolve "the oily liquid and than -filtered. weight of 2-phenyl-'3-pyridolLM. P. 202.34 :to 203 16.1 parts by C. was obtained whichrepresented ado-per cent yield of theory. The :picrate derivative ;after:re-

'cr ysta llizing :from 'alcohol ihad .a melting point of 201.0 to 201.4 C.

Analysis C H N EQNIEQEIEIM CnHaON:

Theory 77.1w 5.26. 3.19 .171. Found 77.48 5.51 3.12 $222332;-

4 EXAMPLE 5 Preparation :of 2 gfi-dimethyL3-pyxidol To 30 parts by weight of 2-acetyl-5-methyl- "furan were added 360 and 500 parts by volume :of'2B,% ammonium hydroxide and ethanol respectively. After heating the mixture for about 20 hours at a temperature of to C. in

.an autoclave, .it was treated with 30 parts by weight of activated carbon in 3 equal increments and then concentrated at reduced pressure on a steam bath until the mixture separated into ithree phases consisting of crystalline, dark oilyliquid, and aqueous phases.

. Neutral Analysis G H N y E quivalcm canon:

" Theory 68.27' 7. 37 11138 1'23.

Found 67.90 7. 55' 11.20' 5122 as'base.

Although .the present invention has been described in conjunction with preferred embodiments,. it is to be understood that modifications and variations .may 'be resorted 'to without departing from the spirit .andscope of the invention,..as .those skilled .in the art will .readily understand. .As for example, .addition .to the acylfurans enumerated .in the specific examples, highermembers. of .theihomologous series .such as .butyryl, .valeryl, caproyl Iurans, etc., may .he treated with ammonia in .a similar manner .to produce .the corresponding .3 pyridols. .As anotherexample, the use of .activatedearbon isnot .the only method forpurification, but other puri- .fication methods can .beusedas will .be apparent .to.those.skilled.in the .art. Since the only purposeof the activatedcarbon was as a purification vagentand thus facilitating the recovery of the final product, its use may be dispensed with .if desired. Such variations and modifications .are considered to be within the purview and scope of .the appended claims.

We claim:

.1. A=processfor the production of a. 3-pyridol which consists .in reactinga 2-acylfuran of the general formula:

. .0 i it 0 wherein R isan alkyl radical containing not more general formula:

o H O/C-R wherein R is an alkyl radical containing not more than two carbon atoms with ammonia at a temperature of 100-200 C. in the presence of water as a solvent.

4. A process for the production of a 3-pyridol which consists in reacting a 2-acy1furan of the general formula:

o H CR wherein R is an alkyl radical containing not more than two carbon atoms with ammonia at a temperature of 200 C. in the presence of alcohol as a solvent.

5. A process for the preparation of Z-methyl- 3-pyrido1 which consists in reacting Z-acetylfuran with ammonia at a temperature of 100 to 200 C. in the presence of water as a solvent.

6. A process for the preparation of 2-ethy1-3- pyridol which consists in reacting Z-propionylfuran with ammonia at a temperature of 100 to 200 C. in the presence of water as a solvent.

ANDREW P. DUNLOP. SAMUEL SWADESH.

References Cited in the file Of this patent UNITED STATES PATENTS Name Date McNally Aug. 29, 1939 OTHER REFERENCES Number 

1. A PROCESS FOR THE PRODUCTION OF A 3-PYRIDOL WHICH CONSISTS IN RACTING A 2-ACYLFURAN OF THE GENERAL FORMULA: 